Substantial replacement of lactose with fat in a high-lactose milk replacer diet increases liver fat accumulation but does not affect insulin sensitivity in veal calves

Abstract

In veal calves, the major portion of digestible energy intake originates from milk replacer (MR), with lactose and fat contributing approximately 45 and 35%, respectively. In veal calves older than 4 mo, prolonged high intakes of MR may lead to problems with glucose homeostasis and insulin sensitivity, ultimately resulting in sustained insulin resistance, hepatic steatosis, and impaired animal performance. The contribution of each of the dietary energy sources (lactose and fat) to deteriorated glucose homeostasis and insulin resistance is currently unknown. Therefore, an experiment was designed to compare the effects of a high-lactose and a high-fat MR on glucose homeostasis and insulin sensitivity in veal calves. Sixteen male Holstein-Friesian calves (120±2.8kg of BW) were assigned to either a high-lactose (HL) or a high-fat (HF) MR for 13 consecutive weeks. After at least 7 wk of adaptation, whole-body insulin sensitivity and insulin secretion were assessed by euglycemic-hyperinsulinemic and hyperglycemic clamps, respectively. Postprandial blood samples were collected to assess glucose, insulin, and triglyceride responses to feeding, and 24-h urine was collected to quantify urinary glucose excretion. At the end of the trial, liver and muscle biopsies were taken to assess triglyceride contents in these tissues. Long-term exposure of calves to HF or HL MR did not affect whole-body insulin sensitivity (averaging 4.2±0.5×10 [(mg/kg∙min)/(μU/mL)]) and insulin secretion. Responses to feeding were greater for plasma glucose and tended to be greater for plasma insulin in HL calves than in HF calves. Urinary glucose excretion was substantially higher in HL calves (75±13g/d) than in HF calves (21±6g/d). Muscle triglyceride content was not affected by treatment and averaged 4.5±0.6g/kg, but liver triglyceride content was higher in HF calves (16.4±0.9g/kg) than in HL calves (11.2±0.7g/kg), indicating increased hepatic fat accumulation. We conclude that increasing the contribution of fat to the digestible energy intake from the MR from 20 to 50%, at the expense of lactose does not affect whole-body insulin sensitivity and insulin secretion in calves. However, a high-lactose MR increases postprandial glucose and insulin responses, whereas a high-fat MR increases fat accumulation in liver but not muscle.

The use of metabolic profiling to identify insulin resistance in veal calves

“…Insulin sensitivity ranged from 1.5 to 8.3 x 10 −2 (mg/(kg*min))/(μU/mL) between calves and was not differentially affected by dietary treatment ( P >0.05; [6]). 50% of all calves had an insulin sensitivity (M/I-value) <4.4 and thus were considered insulin resistant ( IR ).…”

“…A detailed description of the experimental design, diets and feeding were described previously [6]. Briefly, calves were assigned to either a high-lactose diet (HL; n = 8) or a high-fat diet (HF; n = 8), and to 1 of 8 blocks (pairs of calves) with one HL calf and one HF calf per block.…”

“…A detailed description of the experimental procedures were given elsewhere [6]. In short, whole-body insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp technique in seven consecutive weeks (i.e.…”

“…In addition, a substantial decrease in insulin sensitivity is observed in calves during the first months of life [4, 5]. In a recent study with heavy veal calves raised on a high-fat or high-lactose MR diet we observed that insulin sensitivity values were low (averaging 4.2 ± 0.5 x 10 −2 [(mg/(kg*min))/(μU/mL)]), and 50% of the calves develop insulin resistance (when comparing insulin sensitivity values with human cut-off values for defining insulin resistance; [6]). In order to prevent the development of insulin resistance, it is of importance to understand the patho-physiological mechanisms of insulin resistance and to identify early biomarkers of decreased insulin sensitivity.…”

Дієтотерапія У Дітей При Ожирінні, Асоційованому З Лактазною Недостатністю Дорослого Типу

“…Показано, що в клітинних культурах в присутності лактози спостерігається високий рівень секреції IFN-γ і IL-17 [13]. В експериментальному дослідженні було встановлено, що надлишок лак-този в дієті супроводжується розвитком інсуліноре-зистентності [14]. Таким чином, надлишок лактози в дієті, особливо в індивідуумів з ожирінням, може бути ключовим фактором розвитку низькорівневого запалення і інсулінорезистентності, у зв'язку з чим ми вважаємо, що контроль над споживанням лакто-зи в дітей, хворих на ожиріння, може запобігти фор-муванню ускладнень даного захворювання.…”